LONG-TERM FOLLOW-UP AFTER HIGH-DOSE THERAPY FOR HIGH-RISK MULTIPLE-MYELOMA

Between 1985 and 1990, 133 patients with advanced multiple myeloma (MM ) (74% resistance; 41% resistant relapse, RR) were treated with five h igh-dose therapy (HDT) regimens including: melphalan less than or equa l to 100 mg/m(2) (MEL 100) (46 patients); MEL 100 plus GM-CSF (24 pati ents); MEL 140 plus autologous bone marrow transplantation (ABMT) (eig ht patients); MEL 140 plus TBI 850 cGy plus ABMT (37 patients); and th iotepa 750 mg/m(2) (THIO 750) + TBI 850 cGy plus ABMT (18 patients), T he median follow-up of alive patients as of December 1997 was 9 years. Overall, 17% experienced treatment-related mortality within 60 days ( TRM) and 12% achieved stringently defined complete remission (CR) with a median duration of 16 months; four of 16 patients (25%) remain in C R at 10 years. The median durations of event-free survival (EFS)/overa ll survival (OS) were 6/15 months, Superior EFS/OS were noted with MEL 100 plus GM-CSF and the two TBI-containing regimens (9/24 months amon g 79 patients) compared to the remaining 54 patients receiving MEL les s than or equal to 100 or MEL 140 plus ABMT (3/5 months) (P = 0.0001/0 .0001, respectively). Multivariate regression analyses (MVA) were perf ormed so that, despite patient heterogeneity among the five treatment groups, potentially relevant disease, host, treatment, and supportive care variables could be identified that were associated with TRM, CR, EFS and OS, TRM was higher with creatinine >2.0 mg/dl, absence of ABMT /GM-CSF support and age >50 years; CR was superior with TBI-containing regimens and less than or equal to 12 months of prior therapy; EFS an d OS both were longer with B2M less than or equal to 2.5 mg/l, age les s than or equal to 50 years, absence of RR and with ABMT/GM-CSF suppor t. In the presence of >2 favorable variables (32% of patients), median EFS/OS durations of 18/48 months were observed which progressively de clined with 2 and <2 favorable parameters to 6/11 months (28% of patie nts) to 3/5 months (40% of patients) (P = 0.0001/0.0001). At 10 years, 10 and 20% of patients with >2 favorable variables were event-free an d alive, which was also true for the 37 patients receiving MEL 140 plu s TBI. To appreciate possible long-term contributions of supportive ca re or treatment intensity, landmark analyses performed at 1, 2, 4 and 6 months revealed virtually identical ranking orders of prognostically favorable variables to those seen pre-HDT; once supportive care was a ccounted for, regimen intensity with added TBI did not emerge as an in dependent favorable feature.